11-121563719-T-C

Position:

• chr11-121563719-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003105.6(SORL1):​c.3050-3221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 152,326 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.032 (128 hom., cov: 32)
• Consequence: SORL1 NM_003105.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

SORL1 (HGNC:11185): (sortilin related receptor 1) This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10) domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded preproprotein is proteolytically processed to generate the mature receptor, which likely plays roles in endocytosis and sorting. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORL1	NM_003105.6	c.3050-3221T>C		intron_variant		ENST00000260197.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORL1	ENST00000260197.12	c.3050-3221T>C		intron_variant		1	NM_003105.6	P1

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4925 AN: 152208 Hom.: 128 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.00790

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0324 AC: 4930 AN: 152326 Hom.: 128 Cov.: 32 AF XY: 0.0314 AC XY: 2339 AN XY: 74488

Gnomad4 AFR AF: 0.0650

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0759

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.00790

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0298 Hom.: 14

Bravo AF: 0.0348

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11218342; hg19: chr11-121434428;